title: Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours.
abstract: BACKGROUND
  Cisplatin cures over 80% of testicular germ cell tumours (TGCTs), and nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. We explored the association between NER proteins and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) of patients with non-seminomatous (ns)-TGCTs.
  
  
  METHODS
  The expression of ERCC1 and XPA and the presence of γH2AX were evaluated in cancer cell lines and in fresh ns-TGCTs. The ERCC1 protein was also determined in ns-TGCTs. The differences between CPS and non-CPS cell lines and patients were analysed by Student's t- or χ(2)-tests. The differences in OS were analysed using the log-rank test, and the hazard ratios (HRs) were calculated using the Cox model.
  
  
  RESULTS
  High ERCC1 expression was observed in the non-CPS cells, and both ERCC1 and γH2AX expressions were augmented after cisplatin treatment. Increased ERCC1 expression was also identified in non-CPS patients. Neither polymorphism was associated with either CPS or OS. The presence of ERCC1 was associated with non-CPS (P=0.05) and adjusted in the prognosis groups. The HR in ERCC1-negative and non-CPS patients was >14.43, and in ERCC1-positive and non-CPS patients the HR was >11.86 (P<0.001).
  
  
  CONCLUSIONS
  High levels of ERCC1 were associated with non-CPS, suggesting that ERCC1 could be used as a potential indicator of the response to cisplatin and prognosis in ns-TGCTs.
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología (INCan)-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Avenida San Fernando 22, México D.F. 14080, México.
authors.forename: J
authors.initials: J
authors.lastname: Mendoza
authors.forename: J
authors.initials: J
authors.lastname: Martínez
authors.forename: C
authors.initials: C
authors.lastname: Hernández
authors.forename: D
authors.initials: D
authors.lastname: Pérez-Montiel
authors.forename: C
authors.initials: C
authors.lastname: Castro
authors.forename: E
authors.initials: E
authors.lastname: Fabián-Morales
authors.forename: M
authors.initials: M
authors.lastname: Santibáñez
authors.forename: R
authors.initials: R
authors.lastname: González-Barrios
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Chávez
authors.forename: M A
authors.initials: MA
authors.lastname: Andonegui
authors.forename: N
authors.initials: N
authors.lastname: Reynoso
authors.forename: L F
authors.initials: LF
authors.lastname: Oñate
authors.forename: M A
authors.initials: MA
authors.lastname: Jiménez
authors.forename: M
authors.initials: M
authors.lastname: Núñez
authors.forename: R
authors.initials: R
authors.lastname: Dyer
authors.forename: L A
authors.initials: LA
authors.lastname: Herrera
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics*; D006657:Histones / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D009919:Orchiectomy; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D051760:Xeroderma Pigmentosum Group A Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin